title: Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.
abstract: Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions.
authors.affiliation: Division of Endocrinology and Metabolism, Asan Medical Center, Seoul, South Korea.
authors.forename: Mi-Seon
authors.initials: MS
authors.lastname: Shin
authors.forename: Hyukki
authors.initials: H
authors.lastname: Chang
authors.forename: Churl
authors.initials: C
authors.lastname: Namkoong
authors.forename: Gil Myoung
authors.initials: GM
authors.lastname: Kang
authors.forename: Hyun-Kyong
authors.initials: HK
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Gil
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Yu
authors.forename: Kyeong Han
authors.initials: KH
authors.lastname: Park
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D051152:Clusterin / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000097:blood / Q000517:prevention & control / Q000523:psychology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C498500:Clu protein, rat; D051152:Clusterin; D018377:Neurotransmitter Agents; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone